This invention relates to a pharmaceutical composition containing the aconitane derivatives and the tetrahydroprotoberberine derivatives, and to a method for treating the withdrawal syndrome of drug addicts as well as detoxifying drug addicts.
As used herein, the terms:
"drug" means a substance which may cause addiction or dependence upon continuous use. Included within this term are drugs, such as, opium, morphine, heroine, cocaine, marijuana, as well as amphetamine, and the like; PA1 "dependence" means a physical, physiological or psychological reaction and/or interaction of the drug and person, which results in the person exhibiting or having a forced or compulsive use of the drug without a recognized purpose or need for treating a disease, but rather for the purpose of achieving the desired effect, and/or to avoid withdrawal symptoms as defined hereinafter, which occur when the drug is discontinued or the amount used is reduced; PA1 "withdrawal syndrome" means the symptoms and/or indications exhibited by persons who have dependence on a drug which occur on cessation of such use, and include symptoms, such as, perspiration, lacrimation, yawing, chilling, getting goose flesh, mydriasis, vomiting, diarrhea, abdominalgia, arrbythmia, blood pressure increase, insomnia, furor, tremor and delirium, and the like.
It is reported that there are 50 million drug addicts in the world, and the total volume of drug trade is estimated at about 5 billion U.S. dollars per year. On one hand, drug abuse results in serious damage to the human psyche and body, such as, in the loss of moral integrity, decrease in health level, life shortening, serious withdrawal syndrome after discontinuing drugs, and life endangerment. On the other hand, drug abuse also results in social unstability because the drug addict acts unscrupulously to get drugs and thus become a main source of serious crimes in the world. Consequently, drug abuse has seriously imperiled the progress and safety of human beings. To fight against the detrimental effects of drug abuse, governments all over the world take harsh measures to strictly prohibit drug abuse. However, this problem is getting worse. Therefore, it is very urgent for the world to have a medication and method with improved cure effects and low side effects in order to control and treat drug addiction.
At present, there are three major methods of treatment for addiction in most countries as follows:
1. Gradually Reducing Regimen
The main ingredient of the medication used in this method is dosing a medicament with decreasing amounts of opium. The opium content is decreased gradually at different stages of the treatment until it is zero.
2. Substitution Method
The analgesic methadone is used to treat the drug addict in this method.
3. Therapeutic Use of Other Drugs
There are also some medications used to treat drug addiction, such as, Buprenorphine, Clonidine, Cydazocine, Dihydroetorphine hydrochloride, and the like. However, some of these medications can easily cause nervous derangement and agitation, others will cause the withdrawal syndrome or the syndrome will appear on stopping the administration of the medication.
Clinical practice shows that there are very serious drawbacks in the above three treatments for drug addiction. For example, the regimen of gradually reducing the opium content, requires long periods of treatment. Furthermore, this method cannot result in the drug addicts'fundamentally getting rid of this dependency on drugs, and the proportion of re-abusing after treatment still is high.
In the substitution method, methadone is an analgesic and may also result in drug dependence. For example, the dependence potential of 100 mg of oral methadone is equivalent to that of 10 mg of injected morphine. Also, methadone itself has many side effects, such as, pneumonectasis, immunologic symptoms, impotency, as well as accumulation of the drug in the body leading to intoxication, and, more seriously, blindness in both eyes. Infants born by mothers addicted to methadone are likely to show withdrawal symptoms.
In the other drug therapy described above, the medications may have adverse side effects and some of them may also cause drug dependence. At present, some medications are being tested to treat drug addiction, such as, Abbott 69024, Amantidine, Bupropion, Buprenorphine, Bromocriptine, Buspirone, Carbamazepine (Tegretol), Fluoxetine (Prozac), Flupenthixol, Gepirone, Laam, Mazindol, Naltrexone and Schering 23390 (see ref. Scientific American, Mar. 1991, pp 71-79). A few of them have been proved ineffective and others are under development. Thus, there is an urgent need of drug independence medication having high curative effects and low side effects for the treatment of drug addiction.